868
IL-13-Induced Goblet Cell Antigen Passages (GAP's) are Required for the Acute Onset of a Food-Induced Anaphylactic Reaction
Monday, March 6, 2017: 2:15 PM
Room B314 (Georgia World Congress Center, Building B)
Taeko Noah, PhD, , , , , , , , ,
Rationale: GAPs uptake and transport antigens apical to basolaterally within the small intestine (SI). How food allergens cross the SI epithelium and are delivered to the sub-epithelial immune compartment to initiate the onset of a food-induced anaphylactic (FIA) reaction remains largely unknown. Herein, we examined the food antigen uptake by GAPs and the contribution of this pathway to the onset of a FIA reaction.

Methods: To examine the capability of GAPs to sample SI food antigens in vivo and in vitro we employed clinically relevant food antigens (MFA: peanut, cows milk and egg), pharmacological inhibitors of GAPs (Tropicamide and 8-bromo-cADPR) and human intestinal organoids derived from pluripotent stem cells and performed two photon (2P) microscopy. To define the requirement of GAPs during the induction of FIA, we examined the onset of FIA in mice following GAP-inhibition.

Results: We demonstrate the apical-basolateral translocation of MFA can occur via SI GAPs. We show 1) that murine and human SI GAPs are mediated by cholinergic- and IL-13-induced signals, 2) that food allergic (FA) mice have increased SI GAPs; 3) that SI GAPs in FA mice were dependent on IL-13-induced signals and 4) blockade of IL-13-induced CD38/cADPR-pathway attenuated GAPs in FA mice and that this was associated with reduced food allergen transport, intestinal mast cell activation, and the FIA symptoms.  

Conclusions: These results indicate that the food allergen delivery through IL-13/CD38/cADPR-driven-GAPs plays a critical role in the onset of FIA suggesting that targeting cADPR-driven-GAP as an effective therapy in prevention of a FIA reaction.